US20090297641A1 - Herbal compositions for the treatment of mucosal lesions - Google Patents
Herbal compositions for the treatment of mucosal lesions Download PDFInfo
- Publication number
- US20090297641A1 US20090297641A1 US12/417,106 US41710609A US2009297641A1 US 20090297641 A1 US20090297641 A1 US 20090297641A1 US 41710609 A US41710609 A US 41710609A US 2009297641 A1 US2009297641 A1 US 2009297641A1
- Authority
- US
- United States
- Prior art keywords
- extracts
- treatment
- lesions
- matrix metalloproteinases
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 134
- 230000009854 mucosal lesion Effects 0.000 title claims description 15
- 239000000284 extract Substances 0.000 claims abstract description 78
- 241000196324 Embryophyta Species 0.000 claims abstract description 67
- 240000004530 Echinacea purpurea Species 0.000 claims abstract description 33
- 240000006028 Sambucus nigra Species 0.000 claims abstract description 33
- 235000014134 echinacea Nutrition 0.000 claims abstract description 32
- 235000008995 european elder Nutrition 0.000 claims abstract description 32
- 235000003142 Sambucus nigra Nutrition 0.000 claims abstract description 31
- 244000146462 Centella asiatica Species 0.000 claims abstract description 28
- 201000010099 disease Diseases 0.000 claims abstract description 28
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 28
- 235000004032 Centella asiatica Nutrition 0.000 claims abstract description 27
- 240000007311 Commiphora myrrha Species 0.000 claims abstract description 22
- 244000141009 Hypericum perforatum Species 0.000 claims abstract description 22
- 235000017309 Hypericum perforatum Nutrition 0.000 claims abstract description 22
- 235000006965 Commiphora myrrha Nutrition 0.000 claims abstract description 21
- 230000003612 virological effect Effects 0.000 claims abstract description 17
- 102000002274 Matrix Metalloproteinases Human genes 0.000 claims description 57
- 108010000684 Matrix Metalloproteinases Proteins 0.000 claims description 57
- 238000000034 method Methods 0.000 claims description 46
- 230000003902 lesion Effects 0.000 claims description 29
- 239000000419 plant extract Substances 0.000 claims description 27
- 244000052707 Camellia sinensis Species 0.000 claims description 20
- 235000006468 Thea sinensis Nutrition 0.000 claims description 20
- 206010040882 skin lesion Diseases 0.000 claims description 19
- 231100000444 skin lesion Toxicity 0.000 claims description 19
- 241000607122 Uncaria tomentosa Species 0.000 claims description 18
- 235000011472 cat’s claw Nutrition 0.000 claims description 18
- 230000002401 inhibitory effect Effects 0.000 claims description 15
- 208000028169 periodontal disease Diseases 0.000 claims description 15
- 208000014674 injury Diseases 0.000 claims description 14
- 230000008733 trauma Effects 0.000 claims description 14
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 208000002399 aphthous stomatitis Diseases 0.000 claims description 11
- 210000001519 tissue Anatomy 0.000 claims description 11
- 240000002234 Allium sativum Species 0.000 claims description 10
- 240000001432 Calendula officinalis Species 0.000 claims description 10
- 235000005881 Calendula officinalis Nutrition 0.000 claims description 10
- 240000001238 Gaultheria procumbens Species 0.000 claims description 10
- 235000007297 Gaultheria procumbens Nutrition 0.000 claims description 10
- 241000331121 Krameria lappacea Species 0.000 claims description 10
- 241000244355 Ligusticum Species 0.000 claims description 10
- 244000042664 Matricaria chamomilla Species 0.000 claims description 10
- 235000007232 Matricaria chamomilla Nutrition 0.000 claims description 10
- 244000062730 Melissa officinalis Species 0.000 claims description 10
- 235000010654 Melissa officinalis Nutrition 0.000 claims description 10
- 241001278097 Salix alba Species 0.000 claims description 10
- 240000002657 Thymus vulgaris Species 0.000 claims description 10
- 235000007303 Thymus vulgaris Nutrition 0.000 claims description 10
- 241001441361 Usnea barbata Species 0.000 claims description 10
- 235000017537 Vaccinium myrtillus Nutrition 0.000 claims description 10
- 244000078534 Vaccinium myrtillus Species 0.000 claims description 10
- 235000004611 garlic Nutrition 0.000 claims description 10
- 239000001585 thymus vulgaris Substances 0.000 claims description 10
- 230000007794 irritation Effects 0.000 claims description 9
- 206010034277 Pemphigoid Diseases 0.000 claims description 6
- 208000000594 bullous pemphigoid Diseases 0.000 claims description 6
- 208000007565 gingivitis Diseases 0.000 claims description 6
- 201000011486 lichen planus Diseases 0.000 claims description 6
- 210000004877 mucosa Anatomy 0.000 claims description 6
- 206010002153 Anal fissure Diseases 0.000 claims description 5
- 208000016583 Anus disease Diseases 0.000 claims description 5
- 206010012468 Dermatitis herpetiformis Diseases 0.000 claims description 5
- 208000009531 Fissure in Ano Diseases 0.000 claims description 5
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 claims description 5
- 201000011152 Pemphigus Diseases 0.000 claims description 5
- 208000014617 hemorrhoid Diseases 0.000 claims description 5
- 201000001976 pemphigus vulgaris Diseases 0.000 claims description 5
- 230000000306 recurrent effect Effects 0.000 claims description 5
- 208000019751 Anorectal disease Diseases 0.000 claims description 4
- 208000025157 Oral disease Diseases 0.000 claims description 4
- 210000000214 mouth Anatomy 0.000 claims description 4
- 210000004392 genitalia Anatomy 0.000 claims description 3
- 238000000338 in vitro Methods 0.000 claims description 3
- 208000009889 Herpes Simplex Diseases 0.000 claims description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 23
- 230000002757 inflammatory effect Effects 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 52
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 20
- 230000000840 anti-viral effect Effects 0.000 description 20
- 230000000694 effects Effects 0.000 description 20
- 238000002360 preparation method Methods 0.000 description 17
- 238000009472 formulation Methods 0.000 description 12
- 239000000399 hydroalcoholic extract Substances 0.000 description 12
- 238000000605 extraction Methods 0.000 description 11
- 210000002200 mouth mucosa Anatomy 0.000 description 10
- 239000004480 active ingredient Substances 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 208000006877 Insect Bites and Stings Diseases 0.000 description 8
- 239000012676 herbal extract Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 230000000699 topical effect Effects 0.000 description 8
- 102000005741 Metalloproteases Human genes 0.000 description 7
- 108010006035 Metalloproteases Proteins 0.000 description 7
- 102000035195 Peptidases Human genes 0.000 description 7
- 108091005804 Peptidases Proteins 0.000 description 7
- 239000004365 Protease Substances 0.000 description 7
- 239000000872 buffer Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 239000004615 ingredient Substances 0.000 description 6
- 238000007726 management method Methods 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- 229920002125 Sokalan® Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000002500 effect on skin Effects 0.000 description 4
- 229940088598 enzyme Drugs 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 235000019634 flavors Nutrition 0.000 description 4
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 4
- 235000019359 magnesium stearate Nutrition 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 241000700588 Human alphaherpesvirus 1 Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 230000002411 adverse Effects 0.000 description 3
- -1 but not limited to Substances 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 239000002324 mouth wash Substances 0.000 description 3
- 210000004400 mucous membrane Anatomy 0.000 description 3
- 230000003239 periodontal effect Effects 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 231100000419 toxicity Toxicity 0.000 description 3
- 230000001988 toxicity Effects 0.000 description 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 2
- 206010061978 Genital lesion Diseases 0.000 description 2
- 208000034619 Gingival inflammation Diseases 0.000 description 2
- 241000701074 Human alphaherpesvirus 2 Species 0.000 description 2
- 206010028034 Mouth ulceration Diseases 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 239000007983 Tris buffer Substances 0.000 description 2
- 208000025865 Ulcer Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 240000008042 Zea mays Species 0.000 description 2
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 2
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 2
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- 229960001631 carbomer Drugs 0.000 description 2
- 239000000969 carrier Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 238000004113 cell culture Methods 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 235000015218 chewing gum Nutrition 0.000 description 2
- 238000004040 coloring Methods 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 235000005822 corn Nutrition 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000018109 developmental process Effects 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 241000411851 herbal medicine Species 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 230000008289 pathophysiological mechanism Effects 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- YBYRMVIVWMBXKQ-UHFFFAOYSA-N phenylmethanesulfonyl fluoride Chemical compound FS(=O)(=O)CC1=CC=CC=C1 YBYRMVIVWMBXKQ-UHFFFAOYSA-N 0.000 description 2
- 229920000642 polymer Polymers 0.000 description 2
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000000600 sorbitol Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 231100000397 ulcer Toxicity 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 239000001993 wax Substances 0.000 description 2
- QZTKDVCDBIDYMD-UHFFFAOYSA-N 2,2'-[(2-amino-2-oxoethyl)imino]diacetic acid Chemical compound NC(=O)CN(CC(O)=O)CC(O)=O QZTKDVCDBIDYMD-UHFFFAOYSA-N 0.000 description 1
- GHCZTIFQWKKGSB-UHFFFAOYSA-N 2-hydroxypropane-1,2,3-tricarboxylic acid;phosphoric acid Chemical compound OP(O)(O)=O.OC(=O)CC(O)(C(O)=O)CC(O)=O GHCZTIFQWKKGSB-UHFFFAOYSA-N 0.000 description 1
- 239000007988 ADA buffer Substances 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N Acrylic acid Chemical compound OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 208000031295 Animal disease Diseases 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 206010006555 Bullous conditions Diseases 0.000 description 1
- 241000167550 Centella Species 0.000 description 1
- 241000867607 Chlorocebus sabaeus Species 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 244000133098 Echinacea angustifolia Species 0.000 description 1
- 206010015150 Erythema Diseases 0.000 description 1
- 241000546188 Hypericum Species 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 241000218922 Magnoliophyta Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 102000000424 Matrix Metalloproteinase 2 Human genes 0.000 description 1
- 108010016165 Matrix Metalloproteinase 2 Proteins 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000007457 Oral Manifestations Diseases 0.000 description 1
- 208000007117 Oral Ulcer Diseases 0.000 description 1
- 241000721454 Pemphigus Species 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000208829 Sambucus Species 0.000 description 1
- 241000700584 Simplexvirus Species 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 241000157352 Uncaria Species 0.000 description 1
- 240000006064 Urena lobata Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- NCHJGQKLPRTMAO-XWVZOOPGSA-N [(2R)-2-[(2R,3R,4S)-3,4-dihydroxyoxolan-2-yl]-2-hydroxyethyl] 16-methylheptadecanoate Chemical compound CC(C)CCCCCCCCCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NCHJGQKLPRTMAO-XWVZOOPGSA-N 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000012675 alcoholic extract Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- WNROFYMDJYEPJX-UHFFFAOYSA-K aluminium hydroxide Chemical compound [OH-].[OH-].[OH-].[Al+3] WNROFYMDJYEPJX-UHFFFAOYSA-K 0.000 description 1
- 230000003444 anaesthetic effect Effects 0.000 description 1
- 230000000202 analgesic effect Effects 0.000 description 1
- 230000001363 autoimmune Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 239000000378 calcium silicate Substances 0.000 description 1
- 229910052918 calcium silicate Inorganic materials 0.000 description 1
- OYACROKNLOSFPA-UHFFFAOYSA-N calcium;dioxido(oxo)silane Chemical compound [Ca+2].[O-][Si]([O-])=O OYACROKNLOSFPA-UHFFFAOYSA-N 0.000 description 1
- 230000007541 cellular toxicity Effects 0.000 description 1
- 239000013043 chemical agent Substances 0.000 description 1
- 229940112822 chewing gum Drugs 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000037319 collagen production Effects 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 208000002925 dental caries Diseases 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 235000002864 food coloring agent Nutrition 0.000 description 1
- 230000036449 good health Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 235000008216 herbs Nutrition 0.000 description 1
- 238000010191 image analysis Methods 0.000 description 1
- 229940088592 immunologic factor Drugs 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 239000004816 latex Substances 0.000 description 1
- 229920000126 latex Polymers 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 231100000324 minimal toxicity Toxicity 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000030194 mouth disease Diseases 0.000 description 1
- 229940051866 mouthwash Drugs 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 230000007505 plaque formation Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 239000011253 protective coating Substances 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002356 single layer Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000021092 sugar substitutes Nutrition 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 229940034610 toothpaste Drugs 0.000 description 1
- 239000000606 toothpaste Substances 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000820 toxicity test Toxicity 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 241001529453 unidentified herpesvirus Species 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/23—Apiaceae or Umbelliferae (Carrot family), e.g. dill, chervil, coriander or cumin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/32—Burseraceae (Frankincense family)
- A61K36/328—Commiphora, e.g. mecca myrrh or balm of Gilead
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/35—Caprifoliaceae (Honeysuckle family)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
- A61K36/18—Magnoliophyta (angiosperms)
- A61K36/185—Magnoliopsida (dicotyledons)
- A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0031—Rectum, anus
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- the present invention relates to herbal compositions useful for the treatment of mucosal lesions. Although primarily intended for oral use the composition may also be used on the labial, genital and other mucosal surfaces, as well as on the skin.
- plant extracts may be highly effective agents for the prevention and treatment of disease. This is particularly true when one considers the low toxicity and greatly reduced incidence of adverse effects associated with plant-based medicines as compared with many synthetic or highly purified drugs.
- extracts obtained therefrom exert their activities on a variety of physiologic processes, increasing the range of the desired therapeutic effect.
- Oral diseases constitute a diverse group of conditions that are responsible for much human suffering.
- diseases of the hard tissues of the oral cavity e.g. dental caries
- pathological conditions affecting the oral mucosa and periodontal tissues.
- This group includes the commonly found conditions such as gingivitis, periodontal disease, aphthous ulceration and Herpes simplex lesions, as well as the oral manifestations of the less common vesicular-bullous conditions such as bullous pemphigoid, pemphigus, erytheme multiforme and lichen planus, as well as other autoimmune conditions.
- compositions for the treatment of mucosal diseases having higher efficacy and more rapid onset than compositions previously known in the art.
- compositions having lower toxicity and incidence of adverse effects than pharmaceutical compositions for the treatment of mucosal diseases that have been previously described in the art are provided.
- compositions comprising particular combinations of plant extracts are highly effective in the treatment of certain mucosal lesions, particularly those of the oral, anal and genital mucosa, as well as in the treatment of certain skin lesions.
- compositions, medicaments and treatment methods of the present invention which will presently be disclosed, described and exemplified, have been unexpectedly found to cause a dramatic improvement in two significant clinical parameters associated with the mucosal and skin lesions being treated thereby.
- said compositions, medicaments and treatment methods lead to unexpectedly rapid resolution of the mucosal and skin lesions that are being treated.
- the compositions, medicaments and treatment methods of the present invention have also been surprisingly found to cause a dramatic reduction of the pain associated with the mucosal and skin lesions being treated thereby.
- the present invention is primarily directed to a therapeutic composition
- a therapeutic composition comprising extracts of the plant species Echinacea purpurea and Sambucus nigra and the extract(s) of at least one further plant selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica.
- the extract(s) of the at least one further plant are extracts of the plant species Hypericum perforatum and Commiphora molmol.
- composition of the abovementioned preferred embodiment of the composition of the invention is particular directed to an anti-viral composition comprising extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum and Commiphora molmol.
- the above-mentioned anti-viral composition further comprises extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- the above-mentioned anti-viral composition comprises extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa.
- the present invention also provides a therapeutic composition comprising extracts of the plant species Echinacea purpurea and Sambucus nigra together with an extract of the plant species Centella asiatica.
- the immediately preceding therapeutic composition is intended for use in the treatment of diseases of the oral mucosa.
- said therapeutic composition is intended for use in the treatment of an oral mucosal disease selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes.
- the above therapeutic composition is intended for use in the treatment of skin lesions.
- said therapeutic composition is intended for use in the treatment of dermal trauma.
- the therapeutic composition is intended for use in the treatment of insect bites and other local, superficial irritations.
- the above therapeutic composition is intended for use in the treatment of anal lesions.
- said therapeutic composition is intended for use in the treatment of an anal lesion associated with a condition selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- the therapeutic composition for treating mucosal diseases that is disclosed immediately hereinabove be bound to any particular pharmacological or pathophysiological mechanism or mechanisms
- said composition exerts at least some of its desired effects by inhibiting one or more matrix metalloproteinase (MMP) enzymes that are present in the oral mucosal and periodontal tissues, and/or by increasing collagen production at or close to the mucosal site to which said composition is applied.
- MMP matrix metalloproteinase
- said therapeutic compositions may exert at least some of their desired effects by the specific inhibition of certain specific enzymes of the MMP group.
- the therapeutic compositions of the present invention are specific inhibitors of MMP subclasses 1-9, still more specifically of subclasses 1, 2, 8 and 9.
- the invention is also directed to a therapeutic composition
- a therapeutic composition comprising extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica described hereinabove, for the inhibition of one or more matrix metalloproteinases.
- the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1-9. In a more preferred embodiment, said one or more matrix metalloproteinases are selected from the group consisting matrix metalloproteinases 1, 2, 8 and 9. Still more preferably, the matrix metalloproteinase to be inhibited is matrix metalloproteinase 2. In a still further preferred embodiment of this aspect of the present invention, the matrix metalloproteinase-inhibiting therapeutic compositions described immediately hereinabove are intended for use in the treatment of a disease of the oral mucosa selected from the group consisting of periodontal disease and aphthous ulceration.
- the aforementioned therapeutic compositions for treating conditions of the oral or anal mucosal tissues, as well as the aforementioned therapeutic compositions for inhibiting matrix metalloproteinases further comprise extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- the present invention is directed to the use of a combination of extracts of the plant species Echinacea purpurea and Sambucus nigra and of at least one further plant species selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica in the preparation of a medicament.
- the invention is directed to the use of the combination of plant extracts described immediately hereinabove in the preparation of a medicament, wherein said extracts of at least one further plant are extracts of Hypericum perforatum and Commiphora molmol .
- this combination of plant extracts is used in the preparation of an anti-viral medicament.
- the present invention is directed to the use of extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra , in addition to the extracts mentioned hereinabove, in the preparation of an anti-viral medicament.
- extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myr
- the present invention is directed to the use of a combination of extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa in the preparation of an anti-viral medicament.
- the present invention also provides for the use of the above combination of plant extracts in the preparation of a medicament, said extract of at least one further plant being an extract of Centella asiatica .
- this combination of plant extracts is used in the preparation of a medicament for the treatment of a disease of the oral mucosa.
- said disease of the oral mucosa is selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes.
- the invention also provides for the use of the above combination of plant extracts in the preparation of a medicament for the treatment of a skin lesion.
- the skin lesion to be treated is a lesion arising from dermal trauma.
- the skin lesion to be treated is an insect bite.
- the abovementioned combination of plant extracts is used in the preparation of a medicament for the treatment of a disease of the anal mucosa.
- said disease of the anal mucosa is selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- the invention provides for the use of a combination of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica in the preparation of a medicament for inhibiting one or more matrix metalloproteinases.
- said matrix metalloproteinases are selected from the group consisting of matrix metalloproteinases 1 to 9.
- the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1, 2, 8 and 9.
- the abovementioned metalloproteinase-inhibiting medicament is used to treat a disease of the oral mucosa selected from the group consisting of periodontal disease and aphthous ulceration.
- the invention is directed to the use of the above combination of plant extracts in combination with further extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra , in the preparation of medicaments for the treatment of a diseases of the oral and/or anal mucosal tissues, and in the preparation of medicaments for inhibiting the abovementioned one or more matrix metalloproteinases.
- Uncaria tomentosa Thymus vulgaris
- Matricaria recutita Salix alba
- Calendula officinalis Usnea barbata
- the present invention is directed to a combination of extracts of the plant species Echinacea purpurea and Sambucus nigra and of at least one further plant species selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica for use as a medicament.
- the invention is directed to a combination of extracts as disclosed immediately hereinabove, wherein the extracts of the at least one further plant are extracts of Hypericum perforatum and Commiphora molmol .
- the invention is directed to said combination of extracts for use as an anti-viral medicament.
- said combination of extracts is further supplemented by extracts of one or more plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- the invention is directed to a combination of extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa for use as an anti-viral medicament.
- the invention also provides a combination of plant extracts as disclosed hereinabove for use as a medicament, said extract of the at least one further plant being an extract of Centella asiatica .
- this combination of extracts is provided for use as a medicament for the treatment of diseases of the oral mucosa.
- the combination of plant extracts may be used as a medicament for the treatment of many different conditions of the oral mucosa
- the disease to be treated is selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes.
- the combination of plant extracts is provided for use as a medicament for the treatment of skin lesions.
- the skin lesions are lesions arising from dermal trauma.
- the skin lesions are insect bites.
- the aforementioned combination of extracts is provided for use as a medicament for the treatment of diseases of the anal mucosa. While said combination of plant extracts may be used as a medicament for the treatment of many different conditions of the anal mucosa, in a preferred embodiment, the disease to be treated is selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- the above-described combination of extracts is used as a medicament for inhibiting one or more matrix metalloproteinases.
- the one or more matrix metalloproteinases are selected from the group consisting of matrix metalloproteinases 1 to 9. More preferably, said metalloproteinases are selected from the group consisting of matrix metalloproteinases 1, 2, 8 and 9.
- the abovementioned combination of extracts for inhibiting metalloproteinases is used in the treatment of a disease of the oral mucosa selected from the group consisting of periodontal disease and aphthous ulceration.
- the plant extracts used in the aforementioned combination of extracts are further supplemented by extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- the present invention also encompasses a method of treatment of mucosal and/or skin lesions comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea and Sambucus nigra and the extract(s) of at least one further plant selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica to the mucosal lesions and surrounding tissue of a subject in need of such treatment.
- said extracts of at least one further plant are extracts of Hypericum perforatum and Commiphora molmol .
- the lesions to be treated by this method of treatment are viral lesions.
- the present invention also provides a method of treatment of viral lesions as described hereinabove, wherein the aforementioned plant extracts are supplemented by extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- the present invention provides a method of treatment of mucosal and/or skin lesions of viral origin comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa.
- the extract of the at least one further plant is an extract of Centella asiatica .
- the lesions to be treated are oral lesions associated with a disease selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes.
- the lesions to be treated are skin lesions.
- the skin lesions to be treated are lesions arising from dermal trauma.
- the lesions are insect bites.
- the lesions to be treated are anal lesions associated with a disease selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- the present invention is directed to a method of inhibiting one or more matrix metalloproteinases in mucosal and/or skin lesions of a subject in need of such treatment, comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica to said mucosal and/or skin lesions and surrounding tissue.
- the one or more matrix metalloproteinases are selected from the group consisting of matrix metalloproteinases 1 to 9. More preferably, the one or more matrix metalloproteinases are selected from the group consisting of matrix metalloproteinases 1, 2, 8 and 9.
- the aforementioned inhibition of the one or more matrix metalloproteinases is used in the treatment of periodontal disease. In another preferred embodiment, the inhibition of the one or more matrix metalloproteinases is used in the treatment of aphthous ulceration.
- the mixture of plant extracts used may further comprise extracts of plants selected from the group consisting of Gotu kola, Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum portieri - osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of viral lesions of the oral cavity.
- the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of perioral lesions of viral origin.
- the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of genital lesions of viral origin.
- the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of viral lesions caused by the Herpes simplex virus.
- the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of viral lesions of the skin.
- the present invention also encompasses a method for inhibiting one or more matrix metalloproteinases in vitro, comprising contacting an effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica with said one or more matrix metalloproteinases.
- the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1 to 9.
- the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1, 2, 8 and 9.
- FIG. 1 graphically illustrates the reduction in ulcer-associated pain following treatment with an herbal composition of the invention.
- FIG. 2 shows a typical gelatin zymogram indicating the inhibitory effects of composition of the invention on the activity of a mixture of matrix metalloproteinases.
- FIG. 3 graphically illustrates the reduction in insect bite-associated pain and irritation following treatment with an herbal composition of the invention.
- compositions and medicaments of the present invention are based on mixtures of plant extracts.
- extract is used herein to include all of the many types of preparations containing some or all of the active ingredients found in the relevant plants.
- the extracts may be produced by cold extraction techniques using a variety of different extraction solvents including, but not limited to, water, fatty solvents (such as olive oil), and alcoholic solvents (e.g. 70% ethanol).
- Cold extraction techniques are usefully applied to softer parts of the plant such as leaves and flowers, or in cases wherein the desired active components of the plant are heat labile.
- the aforementioned solvents may be used to produce extracts of the desired plants by a hot extraction technique, wherein said solvents are heated to a high temperature, the precise value of said temperature being dependent on the properties of the chosen solvent, and maintained at that temperature throughout the extraction process.
- Hot extraction techniques are more commonly applied to the harder, tougher parts of the plant, such as bark, woody branches and larger roots. In some cases, sequential extractions need to be performed in more than one solvent, and at different temperatures.
- Standard procedures for producing plant extracts are described in many publications including “Medicinal plants: a field guide to the medicinal plants of the Land of Israel (in Hebrew), author: N. Krispil, Har Gilo, Israel, 1986” and “Making plant medicine, author: R. Cech, pub. by Horizon Herbs, 2000”.
- compositions and medicaments containing mixtures of extracts of different plant species may be prepared using different ratios of each extract.
- the antiviral medicaments and compositions of the present invention preferably comprise extracts of Echinacea purpurea, Sambucus nigra, Commiphora molmol and Hypericum perforatum in the following range of weight ratios:
- these components are present in the weight ratio of 4:3:5:4.
- compositions of the invention used to treat mucosal diseases preferably comprise extracts of Centella asiatica, Echinacea purpurea and Sambucus nigra in the following range of weight ratios:
- these extracts are present in the weight ratio of 1.5:1.5:7
- compositions and medicaments of the present invention need to be administered in amounts such that, typically, each topical dose contains between 0.1 mg and 10 mg (dry weight) of each herbal extract, the precise values depending on the particular combination of extracts used, and on the mode of topical delivery.
- weights of the original plant material used to prepare a controlled-release delivery device are:
- Centella asiatica 1.6 mg Echinacea purpurea 1.6 mg Sambucus nigra 7.56 mg
- compositions and medicaments intended primarily for topical use such as those of the present invention
- the compositions and medicaments are to be given by incorporation into a controlled-release intra-oral device (as described in Example 2 hereinbelow)
- said device needs to remain in contact with the lesion to be treated for a period of between 1 and 5 hours. This treatment may be repeated up to 5 times each day, as required, and as determined by a competent clinician.
- Mouthwashes containing the compositions and medicaments of the present invention should be taken in quantities of between 5 ml and 15 ml and allowed to remain in contact with the lesions to be treated for periods of between 30 seconds and one minute. This treatment regime may be repeated up to 5 times per day.
- Lozenges, pastilles, candies and other solid, soluble formulations are to be placed in the mouth, if possible in close proximity to the lesions to be treated, and allowed to dissolve at the natural rate determined by the additives present in said formulations.
- compositions and medicaments of the present invention as disclosed hereinabove and exemplified hereinabove may be prepared and delivered in a number of different forms.
- medicaments and compositions are intended for topical application at the site of the mucosal lesion.
- Dosage forms suitable for topical application to mucosal surfaces include ointments, pastes, lotions, creams, mouthwashes, lozenges, candies, chewing gums, solutions, gels and sprays.
- the compositions of the present invention may also contain excipients such as zinc, zinc oxide, silicones, calcium silicate, aluminum hydroxide, polyethylene glycols, fats of animal or vegetable origin, oils, waxes gums, starch and cellulose or cellulose derivatives.
- compositions for vaginal administration or for anal administration may be prepared by mixing the active plant-derived components with suitable non-toxic, non-irritating carriers such as suppository wax, polyethylene glycol or cocoa butter.
- compositions and medicaments are administered by means of a localized delivery system that allows topical release of the active constituents of said compositions and medicaments.
- a localized delivery system that allows topical release of the active constituents of said compositions and medicaments.
- Any suitable local delivery device may be used to administer the compositions and medicaments to the mucosal surface.
- the local delivery device is a slow release device such as illustrated hereinbelow in Example 2.
- the antiviral composition was prepared as follows: 2 ml of a 1:1 hydroalcoholic extract of Echinacea purpurea was mixed with 7.5 ml of a 1:5 hydroalcoholic extract of Sambucus nigra, 8 ml of a 1:4 hydroalcoholic extract of Commiphora molmol, 10 ml of a 1:4 preparation of a hydroalcoholic extract of Uncaria tomentosa and 20 ml of a 1:10 hydroalcoholic extract of Hypericum perforatum .
- a 1:x hydroalcoholic extract indicates that 1 gram of plant material was extracted with x volumes of the alcoholic extraction medium.
- the extraction medium was a “hydroalcohol”.
- the term “hydroalcohol” is defined as an aqueous solution of a lower alcohol.
- the lower alcohol used was ethanol, which was generally prepared as a 50% solution.
- ethanol was prepared at a different aqueous dilution within the range of 25-90% (v/v), with respect to the ethanol.
- the weight ratio of E. purpurea:S. nigra:C. molmol:U. tomentosa:H. perforatum in this mixture is 4:3:4:5:4.
- the abovementioned alcoholic extracts were purchased either from Herbal Apothecary, Syston, Sheffield, U.K. or from Analit Extracts Ltd, M.P. Hefer 38100, Israel.
- Disks of 3MM filter paper (Whatman Inc.) (5 mm diameter) were soaked in a solution of the compositions to be tested, and placed on a semi-solid agar-containing culture medium covering a monolayer of BSC-1 (green monkey kidney) cells infected with a partially confluent dose of either Herpes simplex type 1 virus (HSV-1) or Herpes simplex type 2 virus (HSV-2). Following 3-4 days incubation at 37° C., the cells were fixed with formaldehyde (20% aqueous solution) and stained with crystal violet (0.1% solution in 0.1M citric acid). The presence of a white color in the central area of the culture indicated toxic damage of the cultured cells due to the anti-viral compositions. Inhibition of viral plaque formation indicated that the composition tested possesses anti-viral activity.
- HSV-1 green monkey kidney
- ACG Acyclovir
- Virosyn is the herbal composition described hereinabove comprising extracts of the following five plant species: Echinacea purpurea, Hypericum perforatum, Commiphora molmol, Uncaria tomentosa and Sambucus nigra.
- Echinacea purpurea Hypericum perforatum
- Commiphora molmol Uncaria tomentosa
- Sambucus nigra The numerical results in the above table are the diameters of the plaques (in mm) after treatment of the cell cultures with the disks soaked with extracts. Each virus inhibition or cell toxicity experiment was performed in triplicate.
- Note 3 The toxicity of each extract was assessed by measuring the diameter of the blue-stained plaque in the center of cell cultures that did not receive virus.
- This example demonstrates the preparation of a slow-release device and the incorporation therein of a plant extract mixture containing Centella, Echinacea and Sambucus.
- the slow release device consists of a mixture of carbomer (carbopol), hydroxypropyl cellulose and magnesium stearate blended as described hereinbelow.
- carbomer carbomer
- hydroxypropyl cellulose hydroxypropyl cellulose
- magnesium stearate magnesium stearate blended as described hereinbelow. Magnesium stearate is used as a protective coating to reduce the solubility and adhesiveness of the device.
- the device is prepared as follows:
- the plant extract mixture is prepared by mixing 6 ml of a 1:4 hydroalcoholic extract of Centella asiatica with 1.5 ml of a 1:1 hydroalcoholic extract of Echinacea purpurea and 35 ml of a 1:5 hydroalcoholic extract of Sambucus nigra .
- the weight ratio of C. asiatica:E. purpurea:S. nigra in this mixture is 15:15:70.
- the hydroalcoholic extracts of Centella asiatica and Echinacea purpurea were purchased from Herbal Apothecary, Syston, Sheffield, U.K., while the hydroalcoholic extract of Sambucus nigra was purchased from Analit Extracts Ltd., M.P. Hefer 38100, Israel.
- extract values of the form 1:x indicate that 1 g of the plant material was dissolved in x liters of solvent.
- hydroalcoholic extract indicates that the plant material was extracted using ethanol at concentrations of between 25% and 50% in water.
- the plant extract mixture is mixed with 2 g sucrose and evaporated to dryness at 40° C. The residue is dissolved in 2 ml water, a further small volume of water added, and the solution lyophilized overnight.
- Magnesium stearate (pharmaceutical grade, obtained from Riedel-De Haen, Germany) (1 g) is mechanically mixed with 2 g of the carbomer-hydroxypropyl cellulose mix.
- step 5. 14 mg of the magnesium stearate-polymer mix (step 5.) is placed on the bottom of the plunger (13 mm diameter die manufactured by Perkin-Elmer, U.K.) of a mechanical press (Spex Industries, Mutuchen, N.J., USA) and overlaid with 70 mg of the plant extract-polymer mix (step 4.). Pressure (10 tons force) is applied for 30 seconds.
- various flavorings, excipients and colorings may be added in order to modify the taste, consistency and color of the preparation.
- the side of the device containing the herbal ingredients (i.e. the side not containing the magnesium stearate) is applied directly to the mucosal surface containing the lesion to be treated.
- the mucosal surface may be pre-moistened with water or saline before application of the device.
- the device is held in place with gentle pressure for approximately 10 seconds. After releasing the gentle pressure, the device adheres to the mucosal tissue for a period of up to five hours.
- the device containing the herbal mixture described hereinabove may be used several times per day (e.g. 3 times per day) for periods of between two days and one month.
- a convenient, non-random sample of 57 dental patients presenting in a private dental clinic with painful oral ulcers of either traumatic or aphthous origin were treated by applying to the affected site a slow-release device containing a herbal composition of the invention (as described in Example 2 hereinabove).
- the device was left in place for a 24 hour period.
- the ulcer-associated pain experienced by the patients was recorded and expressed on a visual analog scale (S. Chrubasik et al. (2000) Am. J. Med. 109: 9-14), as depicted in FIG. 1 .
- the highest recorded pain index reported by an individual patient in this study was 90.
- the effect of the herbal composition used therein on the healing of the oral ulceration experienced by the patients was determined by quantification of lesion size using a Scion image analysis system. Briefly, lesions were photographed and digitized using a digital camera and associated Smartcard. The image files obtained thereby were processed using the Photoshop software package (Adobe Systems Inc.) running in Microsoft Windows ME on an IBM-compatible personal computer. The periphery of each lesion was outlined and copied into a new window of the NIH Image software package (National Institutes of Health, Bethesda, Md.), where, following thresholding, the lesion area was automatically calculated.
- NIH Image software package National Institutes of Health, Bethesda, Md.
- Results from a sequential study of 45 patients with oral ulceration demonstrate that the treatment with the herbal composition caused a mean 60% decrease in lesional size over a 24-36 hour period.
- Protease activity was assessed on gelatin zymograms. Twelve percent polyacrylamide gels (0.75 mm thickness) were cast containing 10% gelatin as a substrate for the collagenase enzymes, which were applied to the gels under non-reducing conditions without heating. The gels were run, soaked in 200 ml of 2% Triton X-100 in distilled water on a gyratory shaker (0.5 hours, 20° C.), and incubated in developing buffer (50 mM Tris [pH 8.0], 1 mM CaCl 2 ), unless otherwise indicated, for 15 hours at 37° C. The gels were examined following staining with Coumassie blue.
- Protease activity shows up as clear bands (indicative of cleavage of the gelatin substrate) on a blue background.
- specific protease inhibitors DFP (1 Mm), EDTA (5 Mm), BBI (10 mg/ml), phenylmethyl sulfonyl fluoride (PMFS) (50 Mm) or tetracyclines (0.1 and 0.25 Mm)
- PMFS phenylmethyl sulfonyl fluoride
- tetracyclines 0.1 and 0.25 Mm
- a composition comprising a mixture of Echinacea purpurea, Sambucus nigra and Centella asiatica (prepared as described in Example 2, hereinabove) were added to the developing buffer after the run but before the gel was incubated in said developing buffer.
- the herbal composition was added to the buffer at a concentration of one volume composition to 50 volumes buffer.
- samples were run on zymograms and subsequently incubated in the appropriate buffer (50 Mm citrate-phosphate buffer [pH 5], 50 Mm ADA buffer [pH 6 and 7], 50 Mm TRIS [pH 8 and 9] or 50 Mm CAPS [pH 10]), containing 1 Mm CaCl 2 .
- a placebo treatment comprising a transmucosal adhesive patch containing food color was used.
- Gingival Tissue removed during periodontal surgery was immediately placed on ice and subsequently frozen and stored at ⁇ 80 degrees C., prior to performing matrix metalloproteinase (MMP) activity analysis thereon, as described hereinabove in Example 5.
- MMP matrix metalloproteinase
- the gingival samples are prepared for this analysis by homogenizing the thawed tissue in PBS and centrifuging [10000 g ⁇ 10 min].
- a subject having a painful insect bite on the skin overlying the upper arm was treated for a period of 24 hours with an adhesive patch comprising a composition containing Echinacea purpurea, Sambucus nigra and Centella asiatica (prepared as described in Example 2, hereinabove).
- the insect bite-associated pain experienced by the patient was recorded and expressed on a visual analog scale, as depicted in FIG. 3 .
- compositions of the invention are given for purposes of illustration and exemplification only, and are not intended to limit the scope of the invention in any way. Thus, both the concentration of active ingredient within each formulation may be changed without removing said formulation from the scope of the invention. Similarly, other formulations comprising the herbal compositions claimed herein that contain different carriers, diluents, excipients, colorings, flavorings and other additives are still to be considered to be within the scope of the present invention.
- Active ingredient used in the following formulation tables refers to any combination of herbal extracts that are within the scope of the invention.
- the weight percentage of the active ingredient is calculated in terms of the dry weight of the herbal composition. Representative examples of such combinations are:
- composition comprising Echinacea purpurea, Hypericum perforatum, Commiphora molmol, Uncaria tomentosa and Sambucus nigra in a weight ratio of 4:4:4:5:3.
- composition comprising Echinacea purpurea, Sambucus nigra and Centella asiatica in a weight ratio of 15:70:15.
- Active ingredient 0.15 Glycerin, U.S.P 10.000 Ethanol, 190-proof, U.S.P 7.500 Flavor 0.040 Polyoxythylene (20) sorbitan monoisostearate 0.200 Sodium saccharin, N.P. 0.050 Boric acid, U.S.P 0.075 FD&C Green (1% solution) 0.045 Distilled water balance
Abstract
Description
- This application is a divisional of U.S. patent application Ser. No. 10/478,718 filed Nov. 24, 2003, which is a U.S. national phase of international application PCT/IL02/00402, filed in English on 22 May 2002, which designated the US. PCT/IL02/00402 claims priority to IL Application No. 143318, filed 23 May 2001. The entire contents of these applications are incorporated herein by reference.
- The present invention relates to herbal compositions useful for the treatment of mucosal lesions. Although primarily intended for oral use the composition may also be used on the labial, genital and other mucosal surfaces, as well as on the skin.
- Historically, the plant world has been the most important source of medicinal agents for the treatment of human and animal disease, and for use as preventative agents in maintaining good health. However, for at least the last 150 years, Western medicine has been dominated by synthetic and/or highly purified chemical agents.
- It is now being increasingly recognized, however, that plant extracts may be highly effective agents for the prevention and treatment of disease. This is particularly true when one considers the low toxicity and greatly reduced incidence of adverse effects associated with plant-based medicines as compared with many synthetic or highly purified drugs. In addition, as the plant possesses a large number of pharmaceutically active agents, extracts obtained therefrom exert their activities on a variety of physiologic processes, increasing the range of the desired therapeutic effect.
- Although traditional reference sources of herbal medicine are valuable guides to the safe and effective use of plant extracts, the appropriate selection and combination of extracted material is still a major challenge to the development of new, highly effective herbal medicines. The scale of this challenge may be more clearly appreciated when it is realized that there are approximately 750,000 species of flowering plants on earth, only very few of which have been scientifically studied for their potential therapeutic value.
- Oral diseases constitute a diverse group of conditions that are responsible for much human suffering. In addition to diseases of the hard tissues of the oral cavity (e.g. dental caries), there are many different pathological conditions affecting the oral mucosa and periodontal tissues. This group includes the commonly found conditions such as gingivitis, periodontal disease, aphthous ulceration and Herpes simplex lesions, as well as the oral manifestations of the less common vesicular-bullous conditions such as bullous pemphigoid, pemphigus, erytheme multiforme and lichen planus, as well as other autoimmune conditions.
- The significance of host-related factors in the pathogenesis of conditions such as periodontal disease is being increasingly recognized. Far from being a passive recipient of pathogenic agents released by plaque bacteria, the host tissues themselves (including the biochemical and immunological factors contained therein) are now known to make an active contribution to disease initiation and progression. One group of host factors which have recently received some attention in relation to the pathogenesis of periodontal disease is the group consisting of various tissue-destroying and tissue-remodelling enzymes. Of particular interest is the large group of matrix metalloproteinases (Page, R. C. (1999) J. Periodont. Res. 34: 331-339). It is now believed that certain, defined, metalloproteinases such as matrix metalloproteinases 1-9 are of particular importance for the development and progression of periodontal disease.
- Although many pharmaceutical agents have been used in the management of mucosal lesions, many of these have been relatively ineffective, while some (in particular, the systemic regimes) are associated with unacceptable adverse effects. There thus exists a need for new, efficacious and safe modes of treatment for many of the aforementioned mucosal diseases. There is a particular need for a safe, effective topical treatment.
- It is a purpose of the present invention to respond to the aforementioned need by providing plant-based compositions for the treatment of mucosal diseases.
- It is another purpose of the invention to provide plant-based anti-viral compositions for use in the treatment of oral and genital lesions.
- It is a further purpose of the invention to provide compositions for the treatment of mucosal diseases having higher efficacy and more rapid onset than compositions previously known in the art.
- It is a still further purpose of the invention to provide compositions having lower toxicity and incidence of adverse effects than pharmaceutical compositions for the treatment of mucosal diseases that have been previously described in the art.
- Further objects and advantages of the present invention will become apparent as the description proceeds.
- It has now been unexpectedly found that certain compositions comprising particular combinations of plant extracts are highly effective in the treatment of certain mucosal lesions, particularly those of the oral, anal and genital mucosa, as well as in the treatment of certain skin lesions. It is to be noted that the compositions, medicaments and treatment methods of the present invention which will presently be disclosed, described and exemplified, have been unexpectedly found to cause a dramatic improvement in two significant clinical parameters associated with the mucosal and skin lesions being treated thereby. Firstly, it has been surprisingly found that said compositions, medicaments and treatment methods lead to unexpectedly rapid resolution of the mucosal and skin lesions that are being treated. Secondly, the compositions, medicaments and treatment methods of the present invention have also been surprisingly found to cause a dramatic reduction of the pain associated with the mucosal and skin lesions being treated thereby.
- The present invention is primarily directed to a therapeutic composition comprising extracts of the plant species Echinacea purpurea and Sambucus nigra and the extract(s) of at least one further plant selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica.
- In one preferred embodiment of the therapeutic composition of the present invention, the extract(s) of the at least one further plant are extracts of the plant species Hypericum perforatum and Commiphora molmol.
- While it is not intended that the use of the composition of the abovementioned preferred embodiment of the composition of the invention be bound to, or limited by any particular theory regarding its chemical or pharmacological mode of action, the present invention is particular directed to an anti-viral composition comprising extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum and Commiphora molmol.
- In a preferred embodiment of the invention, the above-mentioned anti-viral composition further comprises extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- In a particularly preferred embodiment of the invention, the above-mentioned anti-viral composition comprises extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa.
- The present invention also provides a therapeutic composition comprising extracts of the plant species Echinacea purpurea and Sambucus nigra together with an extract of the plant species Centella asiatica.
- In a preferred embodiment of the invention, the immediately preceding therapeutic composition is intended for use in the treatment of diseases of the oral mucosa. In a more preferred embodiment of the invention, said therapeutic composition is intended for use in the treatment of an oral mucosal disease selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes.
- In a further preferred embodiment, the above therapeutic composition is intended for use in the treatment of skin lesions. In one preferred embodiment of the invention, said therapeutic composition is intended for use in the treatment of dermal trauma. In another preferred embodiment, the therapeutic composition is intended for use in the treatment of insect bites and other local, superficial irritations.
- In a still further preferred embodiment of the invention, the above therapeutic composition is intended for use in the treatment of anal lesions. In a more preferred embodiment of the invention, said therapeutic composition is intended for use in the treatment of an anal lesion associated with a condition selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- While it is not intended that the mechanism of action of the therapeutic composition for treating mucosal diseases that is disclosed immediately hereinabove be bound to any particular pharmacological or pathophysiological mechanism or mechanisms, it is believed that said composition exerts at least some of its desired effects by inhibiting one or more matrix metalloproteinase (MMP) enzymes that are present in the oral mucosal and periodontal tissues, and/or by increasing collagen production at or close to the mucosal site to which said composition is applied. In particular, it is believed that said therapeutic compositions may exert at least some of their desired effects by the specific inhibition of certain specific enzymes of the MMP group. More specifically, it is believed that the therapeutic compositions of the present invention are specific inhibitors of MMP subclasses 1-9, still more specifically of
subclasses - Thus, the invention is also directed to a therapeutic composition comprising extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica described hereinabove, for the inhibition of one or more matrix metalloproteinases.
- It is to be noted that the term “inhibition of one or more matrix metalloproteinases” as used immediately hereinabove and hereinabove is intended to convey the meaning of the inhibition of the activity of these enzymes on their substrates.
- In a preferred embodiment of this aspect of the invention, the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1-9. In a more preferred embodiment, said one or more matrix metalloproteinases are selected from the group consisting
matrix metalloproteinases matrix metalloproteinase 2. In a still further preferred embodiment of this aspect of the present invention, the matrix metalloproteinase-inhibiting therapeutic compositions described immediately hereinabove are intended for use in the treatment of a disease of the oral mucosa selected from the group consisting of periodontal disease and aphthous ulceration. - In a further preferred embodiment of the invention, the aforementioned therapeutic compositions for treating conditions of the oral or anal mucosal tissues, as well as the aforementioned therapeutic compositions for inhibiting matrix metalloproteinases further comprise extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- In another aspect, the present invention is directed to the use of a combination of extracts of the plant species Echinacea purpurea and Sambucus nigra and of at least one further plant species selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica in the preparation of a medicament.
- In one preferred embodiment, the invention is directed to the use of the combination of plant extracts described immediately hereinabove in the preparation of a medicament, wherein said extracts of at least one further plant are extracts of Hypericum perforatum and Commiphora molmol. Preferably, this combination of plant extracts is used in the preparation of an anti-viral medicament.
- In a further preferred embodiment, the present invention is directed to the use of extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra, in addition to the extracts mentioned hereinabove, in the preparation of an anti-viral medicament.
- In a particularly preferred embodiment the present invention is directed to the use of a combination of extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa in the preparation of an anti-viral medicament.
- The present invention also provides for the use of the above combination of plant extracts in the preparation of a medicament, said extract of at least one further plant being an extract of Centella asiatica. Preferably, this combination of plant extracts is used in the preparation of a medicament for the treatment of a disease of the oral mucosa. In one embodiment of the invention, said disease of the oral mucosa is selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes.
- In another preferred embodiment, the invention also provides for the use of the above combination of plant extracts in the preparation of a medicament for the treatment of a skin lesion. In one preferred embodiment, the skin lesion to be treated is a lesion arising from dermal trauma. In a further preferred embodiment, the skin lesion to be treated is an insect bite.
- In another preferred embodiment of the invention, the abovementioned combination of plant extracts is used in the preparation of a medicament for the treatment of a disease of the anal mucosa. In one embodiment of the invention, said disease of the anal mucosa is selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- In another aspect the invention provides for the use of a combination of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica in the preparation of a medicament for inhibiting one or more matrix metalloproteinases. Preferably, said matrix metalloproteinases are selected from the group consisting of
matrix metalloproteinases 1 to 9. Most preferably, the one or more matrix metalloproteinases to be inhibited are selected from the group consisting ofmatrix metalloproteinases - In a further preferred embodiment, the invention is directed to the use of the above combination of plant extracts in combination with further extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra, in the preparation of medicaments for the treatment of a diseases of the oral and/or anal mucosal tissues, and in the preparation of medicaments for inhibiting the abovementioned one or more matrix metalloproteinases.
- In another aspect, the present invention is directed to a combination of extracts of the plant species Echinacea purpurea and Sambucus nigra and of at least one further plant species selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica for use as a medicament.
- In a preferred embodiment, the invention is directed to a combination of extracts as disclosed immediately hereinabove, wherein the extracts of the at least one further plant are extracts of Hypericum perforatum and Commiphora molmol. In a preferred embodiment, the invention is directed to said combination of extracts for use as an anti-viral medicament. In a further preferred embodiment, said combination of extracts is further supplemented by extracts of one or more plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- In a particularly preferred embodiment, the invention is directed to a combination of extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa for use as an anti-viral medicament.
- The invention also provides a combination of plant extracts as disclosed hereinabove for use as a medicament, said extract of the at least one further plant being an extract of Centella asiatica. Preferably, this combination of extracts is provided for use as a medicament for the treatment of diseases of the oral mucosa. While said combination of plant extracts may be used as a medicament for the treatment of many different conditions of the oral mucosa, in a preferred embodiment, the disease to be treated is selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes. In another preferred embodiment, the combination of plant extracts is provided for use as a medicament for the treatment of skin lesions. In one preferred embodiment, the skin lesions are lesions arising from dermal trauma. In another preferred embodiment, the skin lesions are insect bites. In yet another preferred embodiment, the aforementioned combination of extracts is provided for use as a medicament for the treatment of diseases of the anal mucosa. While said combination of plant extracts may be used as a medicament for the treatment of many different conditions of the anal mucosa, in a preferred embodiment, the disease to be treated is selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- In another aspect, the above-described combination of extracts is used as a medicament for inhibiting one or more matrix metalloproteinases. Preferably, the one or more matrix metalloproteinases are selected from the group consisting of
matrix metalloproteinases 1 to 9. More preferably, said metalloproteinases are selected from the group consisting ofmatrix metalloproteinases - In yet another embodiment of the invention, the plant extracts used in the aforementioned combination of extracts are further supplemented by extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- The present invention also encompasses a method of treatment of mucosal and/or skin lesions comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea and Sambucus nigra and the extract(s) of at least one further plant selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica to the mucosal lesions and surrounding tissue of a subject in need of such treatment. In a preferred embodiment of this method of treatment, said extracts of at least one further plant are extracts of Hypericum perforatum and Commiphora molmol. In a preferred embodiment, the lesions to be treated by this method of treatment are viral lesions.
- In a further preferred embodiment, the present invention also provides a method of treatment of viral lesions as described hereinabove, wherein the aforementioned plant extracts are supplemented by extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- In a particularly preferred embodiment, the present invention provides a method of treatment of mucosal and/or skin lesions of viral origin comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa.
- In another preferred embodiment of the method of the invention, the extract of the at least one further plant is an extract of Centella asiatica. In one preferred embodiment of this aspect of the invention, the lesions to be treated are oral lesions associated with a disease selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes. In another preferred embodiment, the lesions to be treated are skin lesions. In one more preferred embodiment, the skin lesions to be treated are lesions arising from dermal trauma. In a further preferred embodiment, the lesions are insect bites. In another preferred embodiment of this aspect of the invention, the lesions to be treated are anal lesions associated with a disease selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation.
- In a further aspect, the present invention is directed to a method of inhibiting one or more matrix metalloproteinases in mucosal and/or skin lesions of a subject in need of such treatment, comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica to said mucosal and/or skin lesions and surrounding tissue. Preferably, the one or more matrix metalloproteinases are selected from the group consisting of
matrix metalloproteinases 1 to 9. More preferably, the one or more matrix metalloproteinases are selected from the group consisting ofmatrix metalloproteinases - In each of the above-described methods, the mixture of plant extracts used may further comprise extracts of plants selected from the group consisting of Gotu kola, Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra.
- In one preferred embodiment of the invention, the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of viral lesions of the oral cavity.
- In another preferred embodiment of the invention, the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of perioral lesions of viral origin.
- In yet another preferred embodiment of the invention, the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of genital lesions of viral origin.
- In yet another preferred embodiment of the invention, the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of viral lesions caused by the Herpes simplex virus.
- In yet another preferred embodiment of the invention, the anti-viral compositions, medicaments and treatment methods are used in the treatment or management of viral lesions of the skin.
- In another aspect, the present invention also encompasses a method for inhibiting one or more matrix metalloproteinases in vitro, comprising contacting an effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica with said one or more matrix metalloproteinases. In one embodiment of this aspect of the invention, the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of
matrix metalloproteinases 1 to 9. In another embodiment, the one or more matrix metalloproteinases to be inhibited are selected from the group consisting ofmatrix metalloproteinases - All the above and other characteristics and advantages of the present invention will be further understood from the following illustrative and non-limitative examples of preferred embodiments thereof.
-
FIG. 1 graphically illustrates the reduction in ulcer-associated pain following treatment with an herbal composition of the invention. -
FIG. 2 shows a typical gelatin zymogram indicating the inhibitory effects of composition of the invention on the activity of a mixture of matrix metalloproteinases. -
FIG. 3 graphically illustrates the reduction in insect bite-associated pain and irritation following treatment with an herbal composition of the invention. - The compositions and medicaments of the present invention are based on mixtures of plant extracts. It is to be noted that the term “extract” is used herein to include all of the many types of preparations containing some or all of the active ingredients found in the relevant plants. Thus the extracts may be produced by cold extraction techniques using a variety of different extraction solvents including, but not limited to, water, fatty solvents (such as olive oil), and alcoholic solvents (e.g. 70% ethanol). Cold extraction techniques are usefully applied to softer parts of the plant such as leaves and flowers, or in cases wherein the desired active components of the plant are heat labile. Alternatively, the aforementioned solvents may be used to produce extracts of the desired plants by a hot extraction technique, wherein said solvents are heated to a high temperature, the precise value of said temperature being dependent on the properties of the chosen solvent, and maintained at that temperature throughout the extraction process. Hot extraction techniques are more commonly applied to the harder, tougher parts of the plant, such as bark, woody branches and larger roots. In some cases, sequential extractions need to be performed in more than one solvent, and at different temperatures.
- Standard procedures for producing plant extracts (including hot extraction, cold extraction and other techniques) are described in many publications including “Medicinal plants: a field guide to the medicinal plants of the Land of Israel (in Hebrew), author: N. Krispil, Har Gilo, Israel, 1986” and “Making plant medicine, author: R. Cech, pub. by Horizon Herbs, 2000”.
- Compositions and medicaments containing mixtures of extracts of different plant species, such as those of the present invention may be prepared using different ratios of each extract. For example, the antiviral medicaments and compositions of the present invention preferably comprise extracts of Echinacea purpurea, Sambucus nigra, Commiphora molmol and Hypericum perforatum in the following range of weight ratios:
-
- 2-6:2-4:3-6:2-6
- More preferably, these components are present in the weight ratio of 4:3:5:4.
- Similarly, the compositions of the invention used to treat mucosal diseases preferably comprise extracts of Centella asiatica, Echinacea purpurea and Sambucus nigra in the following range of weight ratios:
- 0.5-3:0.5-3:2:15
- More preferably, these extracts are present in the weight ratio of 1.5:1.5:7
- In order to treat a patient with a therapeutic composition or medicament containing a mixture of herbal extracts as described hereinabove, it is necessary to administer said composition or said medicament in a therapeutically-effective amount, that is, in an amount that will provide a concentration of the herbal extracts at the treatment site that is capable of exerting the desired therapeutic effect. It has been found, in general terms, that the compositions and medicaments of the present invention need to be administered in amounts such that, typically, each topical dose contains between 0.1 mg and 10 mg (dry weight) of each herbal extract, the precise values depending on the particular combination of extracts used, and on the mode of topical delivery. Thus, in the case of the therapeutic composition of the present invention that is used in the treatment of mucosal lesions, the weights of the original plant material used to prepare a controlled-release delivery device (as described in Example 2, hereinbelow) are:
- Centella asiatica 1.6 mg
Echinacea purpurea 1.6 mg
Sambucus nigra 7.56 mg - In the case of compositions and medicaments intended primarily for topical use (such as those of the present invention), it is necessary to administer said compositions and medicaments for periods of time that are sufficient to allow optimal contact of the therapeutically effective amounts of the herbal extracts with the lesions to be treated. When the compositions and medicaments are to be given by incorporation into a controlled-release intra-oral device (as described in Example 2 hereinbelow), said device needs to remain in contact with the lesion to be treated for a period of between 1 and 5 hours. This treatment may be repeated up to 5 times each day, as required, and as determined by a competent clinician.
- Mouthwashes containing the compositions and medicaments of the present invention should be taken in quantities of between 5 ml and 15 ml and allowed to remain in contact with the lesions to be treated for periods of between 30 seconds and one minute. This treatment regime may be repeated up to 5 times per day.
- Lozenges, pastilles, candies and other solid, soluble formulations are to be placed in the mouth, if possible in close proximity to the lesions to be treated, and allowed to dissolve at the natural rate determined by the additives present in said formulations.
- The compositions and medicaments of the present invention as disclosed hereinabove and exemplified hereinabove may be prepared and delivered in a number of different forms.
- In a preferred embodiment of the invention, medicaments and compositions are intended for topical application at the site of the mucosal lesion. Dosage forms suitable for topical application to mucosal surfaces include ointments, pastes, lotions, creams, mouthwashes, lozenges, candies, chewing gums, solutions, gels and sprays. Thus, in addition to the active ingredients, the compositions of the present invention may also contain excipients such as zinc, zinc oxide, silicones, calcium silicate, aluminum hydroxide, polyethylene glycols, fats of animal or vegetable origin, oils, waxes gums, starch and cellulose or cellulose derivatives.
- In other embodiments of the invention, compositions for vaginal administration or for anal administration may be prepared by mixing the active plant-derived components with suitable non-toxic, non-irritating carriers such as suppository wax, polyethylene glycol or cocoa butter.
- In a preferred embodiment of the invention, the compositions and medicaments are administered by means of a localized delivery system that allows topical release of the active constituents of said compositions and medicaments. Any suitable local delivery device may be used to administer the compositions and medicaments to the mucosal surface. However, in a particularly preferred embodiment of the invention the local delivery device is a slow release device such as illustrated hereinbelow in Example 2.
- The following examples are provided for illustrative purposes and in order to more particularly explain and describe the present invention. The present invention, however, is not limited to the particular embodiments disclosed in the examples.
- The antiviral composition was prepared as follows: 2 ml of a 1:1 hydroalcoholic extract of Echinacea purpurea was mixed with 7.5 ml of a 1:5 hydroalcoholic extract of Sambucus nigra, 8 ml of a 1:4 hydroalcoholic extract of Commiphora molmol, 10 ml of a 1:4 preparation of a hydroalcoholic extract of Uncaria tomentosa and 20 ml of a 1:10 hydroalcoholic extract of Hypericum perforatum. The term “a 1:x hydroalcoholic extract” as used herein indicates that 1 gram of plant material was extracted with x volumes of the alcoholic extraction medium. In the case of all of the plant extracts used in the present example, the extraction medium was a “hydroalcohol”. For the present purposes, the term “hydroalcohol” is defined as an aqueous solution of a lower alcohol. Preferably, the lower alcohol used was ethanol, which was generally prepared as a 50% solution. In some preparations, ethanol was prepared at a different aqueous dilution within the range of 25-90% (v/v), with respect to the ethanol. The weight ratio of E. purpurea:S. nigra:C. molmol:U. tomentosa:H. perforatum in this mixture is 4:3:4:5:4. The abovementioned alcoholic extracts were purchased either from Herbal Apothecary, Syston, Leicester, U.K. or from Analit Extracts Ltd, M.P. Hefer 38100, Israel.
- Disks of 3MM filter paper (Whatman Inc.) (5 mm diameter) were soaked in a solution of the compositions to be tested, and placed on a semi-solid agar-containing culture medium covering a monolayer of BSC-1 (green monkey kidney) cells infected with a partially confluent dose of either
Herpes simplex type 1 virus (HSV-1) orHerpes simplex type 2 virus (HSV-2). Following 3-4 days incubation at 37° C., the cells were fixed with formaldehyde (20% aqueous solution) and stained with crystal violet (0.1% solution in 0.1M citric acid). The presence of a white color in the central area of the culture indicated toxic damage of the cultured cells due to the anti-viral compositions. Inhibition of viral plaque formation indicated that the composition tested possesses anti-viral activity. - Acyclovir (ACG), a known and commonly used drug against herpes viruses, was included in the assay as a positive control.
- The results of a typical plaque assay are given below.
-
Extract Toxicity anti-HSV1 anti-HSV2 Virosyn 0-10 2-11 3-11 Hypericum 5 4-7 3-12 Uncaria 0 0-8 7-8
Note 1: Virosyn is the herbal composition described hereinabove comprising extracts of the following five plant species: Echinacea purpurea, Hypericum perforatum, Commiphora molmol, Uncaria tomentosa and Sambucus nigra.
Note 2: The numerical results in the above table are the diameters of the plaques (in mm) after treatment of the cell cultures with the disks soaked with extracts. Each virus inhibition or cell toxicity experiment was performed in triplicate.
Note 3: The toxicity of each extract was assessed by measuring the diameter of the blue-stained plaque in the center of cell cultures that did not receive virus. - The above results indicate that the herbal extract mixture tested possess antiviral activity for both HSV1 and with minimal toxicity to the cultured mammalian cells.
- This example demonstrates the preparation of a slow-release device and the incorporation therein of a plant extract mixture containing Centella, Echinacea and Sambucus.
- The slow release device consists of a mixture of carbomer (carbopol), hydroxypropyl cellulose and magnesium stearate blended as described hereinbelow. Magnesium stearate is used as a protective coating to reduce the solubility and adhesiveness of the device.
- The device is prepared as follows:
- 1. The plant extract mixture is prepared by mixing 6 ml of a 1:4 hydroalcoholic extract of Centella asiatica with 1.5 ml of a 1:1 hydroalcoholic extract of Echinacea purpurea and 35 ml of a 1:5 hydroalcoholic extract of Sambucus nigra. The weight ratio of C. asiatica:E. purpurea:S. nigra in this mixture is 15:15:70. The hydroalcoholic extracts of Centella asiatica and Echinacea purpurea were purchased from Herbal Apothecary, Syston, Leicester, U.K., while the hydroalcoholic extract of Sambucus nigra was purchased from Analit Extracts Ltd., M.P. Hefer 38100, Israel. It is be noted that the abovementioned extract values of the form 1:x indicate that 1 g of the plant material was dissolved in x liters of solvent. The term “hydroalcoholic extract” indicates that the plant material was extracted using ethanol at concentrations of between 25% and 50% in water.
- 2. The plant extract mixture is mixed with 2 g sucrose and evaporated to dryness at 40° C. The residue is dissolved in 2 ml water, a further small volume of water added, and the solution lyophilized overnight.
- 3. A mixture of the carbomer compound Carbopol® 934 P (B.F. Goodrich, Cleveland, Ohio, USA) (2 g) and hydroxypropyl cellulose (Klucel Type HF, Hercules BV, Rijswijk, Holland) (1 g) is prepared by crushing the two components together.
- 4. A 1 g aliquot of the carbomer-hydroxypropyl cellulose mix (prepared in
step 3.) is mixed together with 100 mg of the lyophilized plant extract powder (prepared in step 2). - 5. Magnesium stearate (pharmaceutical grade, obtained from Riedel-De Haen, Germany) (1 g) is mechanically mixed with 2 g of the carbomer-hydroxypropyl cellulose mix.
- 6. 14 mg of the magnesium stearate-polymer mix (
step 5.) is placed on the bottom of the plunger (13 mm diameter die manufactured by Perkin-Elmer, U.K.) of a mechanical press (Spex Industries, Mutuchen, N.J., USA) and overlaid with 70 mg of the plant extract-polymer mix (step 4.). Pressure (10 tons force) is applied for 30 seconds. - In addition to the active herbal ingredients, various flavorings, excipients and colorings may be added in order to modify the taste, consistency and color of the preparation.
- The side of the device containing the herbal ingredients (i.e. the side not containing the magnesium stearate) is applied directly to the mucosal surface containing the lesion to be treated. Alternatively, the mucosal surface may be pre-moistened with water or saline before application of the device. Following application, the device is held in place with gentle pressure for approximately 10 seconds. After releasing the gentle pressure, the device adheres to the mucosal tissue for a period of up to five hours.
- Depending on the mucosal lesion to be treated, the device containing the herbal mixture described hereinabove may be used several times per day (e.g. 3 times per day) for periods of between two days and one month.
- A convenient, non-random sample of 57 dental patients presenting in a private dental clinic with painful oral ulcers of either traumatic or aphthous origin were treated by applying to the affected site a slow-release device containing a herbal composition of the invention (as described in Example 2 hereinabove). The device was left in place for a 24 hour period. The ulcer-associated pain experienced by the patients was recorded and expressed on a visual analog scale (S. Chrubasik et al. (2000) Am. J. Med. 109: 9-14), as depicted in
FIG. 1 . The clinical correlates of the pain index values used in this scale are as follows: 0=no pain; 50=requires analgesic; 100=requires anesthetic. The highest recorded pain index reported by an individual patient in this study was 90. - It may be seen from these results that the patients experienced an almost immediate decrease in pain (with a mean decrease of greater than 50%). This decrease in pain levels continued over the following 6 hours, achieving a mean pain decrease of greater than 70%. The painful symptoms did not recur following cessation of treatment.
- Operating as in the study presented in Example 3, the effect of the herbal composition used therein on the healing of the oral ulceration experienced by the patients was determined by quantification of lesion size using a Scion image analysis system. Briefly, lesions were photographed and digitized using a digital camera and associated Smartcard. The image files obtained thereby were processed using the Photoshop software package (Adobe Systems Inc.) running in Microsoft Windows ME on an IBM-compatible personal computer. The periphery of each lesion was outlined and copied into a new window of the NIH Image software package (National Institutes of Health, Bethesda, Md.), where, following thresholding, the lesion area was automatically calculated.
- Results from a sequential study of 45 patients with oral ulceration demonstrate that the treatment with the herbal composition caused a mean 60% decrease in lesional size over a 24-36 hour period.
- Protease activity was assessed on gelatin zymograms. Twelve percent polyacrylamide gels (0.75 mm thickness) were cast containing 10% gelatin as a substrate for the collagenase enzymes, which were applied to the gels under non-reducing conditions without heating. The gels were run, soaked in 200 ml of 2% Triton X-100 in distilled water on a gyratory shaker (0.5 hours, 20° C.), and incubated in developing buffer (50 mM Tris [pH 8.0], 1 mM CaCl2), unless otherwise indicated, for 15 hours at 37° C. The gels were examined following staining with Coumassie blue. Protease activity shows up as clear bands (indicative of cleavage of the gelatin substrate) on a blue background. For inhibition studies, either specific protease inhibitors (DFP (1 Mm), EDTA (5 Mm), BBI (10 mg/ml), phenylmethyl sulfonyl fluoride (PMFS) (50 Mm) or tetracyclines (0.1 and 0.25 Mm)) or a composition comprising a mixture of Echinacea purpurea, Sambucus nigra and Centella asiatica (prepared as described in Example 2, hereinabove) were added to the developing buffer after the run but before the gel was incubated in said developing buffer. In the latter case, the herbal composition was added to the buffer at a concentration of one volume composition to 50 volumes buffer. To determine protease activity as a function of pH, samples were run on zymograms and subsequently incubated in the appropriate buffer (50 Mm citrate-phosphate buffer [pH 5], 50 Mm ADA buffer [
pH 6 and 7], 50 Mm TRIS [pH 8 and 9] or 50 Mm CAPS [pH 10]), containing 1 Mm CaCl2. - Preliminary findings have demonstrated strong inhibitory effects of low concentrations of the herbal extracts on a cocktail of proteases (containing high concentrations of
matrix metalloproteinases - Representative results are shown in the gelatin zymogram depicted in
FIG. 2 , in which active proteases are indicated as white bands on a dark background. Line 1: 50 ng active metalloproteases are clearly detectable.Line 2 demonstrates definitive inhibition of the same metalloprotease cocktail present inline 1 by a 1/50 dilution of the aforementioned herbal composition. - This study forms part of a controlled double-blind matched-sample (sixteen patients), three part clinical trial of the use of a herbal composition of the invention in controlling
gingival inflammation - In the control subjects, a placebo treatment comprising a transmucosal adhesive patch containing food color was used.
- Gingival Tissue removed during periodontal surgery was immediately placed on ice and subsequently frozen and stored at −80 degrees C., prior to performing matrix metalloproteinase (MMP) activity analysis thereon, as described hereinabove in Example 5. The gingival samples are prepared for this analysis by homogenizing the thawed tissue in PBS and centrifuging [10000 g×10 min].
- The preliminary results obtained (data not shown) demonstrate that bands were found in the areas consistent with
MMP - A subject having a painful insect bite on the skin overlying the upper arm was treated for a period of 24 hours with an adhesive patch comprising a composition containing Echinacea purpurea, Sambucus nigra and Centella asiatica (prepared as described in Example 2, hereinabove). The insect bite-associated pain experienced by the patient was recorded and expressed on a visual analog scale, as depicted in
FIG. 3 . The clinical correlates of the pain index values used in this scale are as follows: 0=asymptomatic; 50=requires medication; 100=extreme localized discomfort. The highest recorded pain index reported in this study was 38. - It may be seen from these results that almost instantaneous relief of the localized irritation was obtained.
- The following formulations comprising herbal compositions of the invention are given for purposes of illustration and exemplification only, and are not intended to limit the scope of the invention in any way. Thus, both the concentration of active ingredient within each formulation may be changed without removing said formulation from the scope of the invention. Similarly, other formulations comprising the herbal compositions claimed herein that contain different carriers, diluents, excipients, colorings, flavorings and other additives are still to be considered to be within the scope of the present invention.
- The term “Active ingredient” used in the following formulation tables refers to any combination of herbal extracts that are within the scope of the invention. The weight percentage of the active ingredient is calculated in terms of the dry weight of the herbal composition. Representative examples of such combinations are:
- A) composition comprising Echinacea purpurea, Hypericum perforatum, Commiphora molmol, Uncaria tomentosa and Sambucus nigra in a weight ratio of 4:4:4:5:3.
- B) composition comprising Echinacea purpurea, Sambucus nigra and Centella asiatica in a weight ratio of 15:70:15.
-
-
Ingredient % by weight Active ingredient 0.15 Glycerin, U.S.P 10.000 Ethanol, 190-proof, U.S.P 7.500 Flavor 0.040 Polyoxythylene (20) sorbitan monoisostearate 0.200 Sodium saccharin, N.P. 0.050 Boric acid, U.S.P 0.075 FD&C Green (1% solution) 0.045 Distilled water balance -
-
Ingredient % by weight Active ingredient 0.25 Sorbitol 17.5 Mannitol 17.5 Starch 13.6 Sugar substitute 1.2 Flavor 11.7 Color 0.1 Corn syrup Balance -
-
Ingredient % by weight Active ingredient 0.25 Gum base (30 parts Eastergum, 45 parts Coumarone resin, 30.00 15 parts dry latex, 10 parts Paraffin wax) Sugar 50.00 Corn syrup 18.00 Citric acid 1.00 Flavor balance -
-
Ingredient % by weight Active ingredient 0.5 Sorbitol 33.00 Saccharin 0.46 Silica 22.00 NaF 0.243 Glycerin 9.00 NaOH (50%) 0.20 Carbopol 0.20 Keltrol 0.60 TiO2 0.50 Sodium alkyl sulphate (28% solution) 4.00 PEG 63.00 FD&C Blue# 1 (1% solution) 0.05 Flavor 1.1 Water Balance - While specific embodiments of the invention have been described for the purpose of illustration, it will be understood that the invention may be carried out in practice by skilled persons with many modifications, variations and adaptations, without departing from its spirit or exceeding the scope of the claims.
Claims (21)
- 50. A method of treatment of mucosal lesions comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea and Sambucus nigra and the extract(s) of at least one further plant selected from the group consisting of Hypericum perforatum, Commiphora molmol and Centella asiatica to the mucosal lesions and surrounding tissue of a subject in need of such treatment.
- 51. A method of treatment according to
claim 50 , wherein the extracts of at least one further plant are extracts of Hypericum perforatum and Commiphora molmol. - 52. A method of treatment according to
claim 51 , wherein the mucosal lesions to be treated are viral lesions. - 53. A method of treatment according to
claim 52 , wherein the viral lesions are located in the oral cavity. - 54. A method of treatment according to
claim 52 , wherein the viral lesions are located in the perioral region. - 55. A method of treatment according to
claim 52 , wherein the viral lesions are located in the genital mucosa. - 56. A method of treatment according to
claim 52 , wherein the viral lesions are caused by Herpes simplex. - 57. A method of treatment according to
claim 52 , wherein the mixture of plant extracts further comprises extracts of plants selected from the group consisting of Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra. - 58. A method of treatment according to claim 7, wherein the mixture of plant extracts comprises extracts of the plant species Echinacea purpurea, Sambucus nigra, Hypericum perforatum, Commiphora molmol and Uncaria tomentosa.
- 59. A method of treatment according to
claim 50 , wherein the extract of the at least one further plant is an extract of Centella asiatica. - 60. A method of treatment according to
claim 59 , wherein the mucosal lesions are oral lesions associated with a disease selected from the group consisting of periodontal disease, gingivitis, aphthous ulceration, mechanical trauma, thermal trauma, lichen planus, bullous pemphigoid, pemphigus vulgaris, dermatitis herpetiformis, angular chelitis and recurrent herpes. - 61. A method of treatment according to
claim 59 , wherein the mucosal lesions are anal lesions associated with a disease selected from the group consisting of anal fissures, hemorrhoids and non-specific irritation. - 62. A method of inhibiting one or more matrix metalloproteinases in mucosal and/or skin lesions of a subject in need of such treatment, comprising the application of a therapeutically-effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica to said mucosal and/or skin lesions and surrounding tissue.
- 63. A method according to
claim 62 , wherein the one or more matrix metalloproteinases are selected from the group consisting of matrix metalloproteinases 1 to 9. - 64. A method according to
claim 63 , wherein the one or more matrix metalloproteinases are selected from the group consisting of matrix metalloproteinases 1, 2, 8 and 9. - 65. A method according to any one of
claims 62 ,63 and64 , wherein the inhibition of the one or more matrix metalloproteinases is used in the treatment of periodontal disease. - 66. A method according to any one of
claims 62 ,63 and64 , wherein the inhibition of the one or more matrix metalloproteinases is used in the treatment of aphthous ulceration. - 67. A method according to any one of
claims 59 to66 , wherein the mixture of plant extracts further comprises extracts of plants selected from the group consisting of Gotu kola, Uncaria tomentosa, Thymus vulgaris, Matricaria recutita, Salix alba, Calendula officinalis, Usnea barbata, Ligusticum porterii-osha, Gaultheria procumbens, Camellia sinensis, Vaccinium myrtillus, Melissa officinalis, Allium sativum, Camellia sinensis and Krameria triandra. - 68. A method for inhibiting one or more matrix metalloproteinases in vitro, comprising contacting an effective amount of a mixture of extracts of the plant species Echinacea purpurea, Sambucus nigra and Centella asiatica with said one or more matrix metalloproteinases.
- 69. A method according to
claim 68 , wherein the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1 to 9. - 70. A method according to
claim 69 , wherein the one or more matrix metalloproteinases to be inhibited are selected from the group consisting of matrix metalloproteinases 1, 2, 8 and 9.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US12/417,106 US8075926B2 (en) | 2001-05-23 | 2009-04-02 | Herbal compositions for the treatment of mucosal lesions |
Applications Claiming Priority (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
IL14331801A IL143318A0 (en) | 2001-05-23 | 2001-05-23 | Herbal compositions for the treatment of mucosal lesions |
IL143318 | 2001-05-23 | ||
PCT/IL2002/000402 WO2002094300A1 (en) | 2001-05-23 | 2002-05-22 | Herbal compositions for the treatment of mucosal lesions |
US10/478,718 US7563466B2 (en) | 2001-05-23 | 2002-05-22 | Herbal compositions for the treatment of mucosal lesions |
US12/417,106 US8075926B2 (en) | 2001-05-23 | 2009-04-02 | Herbal compositions for the treatment of mucosal lesions |
Related Parent Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/IL2002/000402 Division WO2002094300A1 (en) | 2001-05-23 | 2002-05-22 | Herbal compositions for the treatment of mucosal lesions |
US10478718 Division | 2002-05-22 | ||
US10/478,718 Division US7563466B2 (en) | 2001-05-23 | 2002-05-22 | Herbal compositions for the treatment of mucosal lesions |
Publications (2)
Publication Number | Publication Date |
---|---|
US20090297641A1 true US20090297641A1 (en) | 2009-12-03 |
US8075926B2 US8075926B2 (en) | 2011-12-13 |
Family
ID=11075430
Family Applications (5)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/478,718 Expired - Lifetime US7563466B2 (en) | 2001-05-23 | 2002-05-22 | Herbal compositions for the treatment of mucosal lesions |
US12/417,106 Expired - Fee Related US8075926B2 (en) | 2001-05-23 | 2009-04-02 | Herbal compositions for the treatment of mucosal lesions |
US12/417,111 Abandoned US20090186104A1 (en) | 2001-05-23 | 2009-04-02 | Herbal compositions for the treatment of mucosal lesions |
US12/941,535 Abandoned US20110052733A1 (en) | 2001-05-23 | 2010-11-08 | Herbal compositions for the treatment of mucosal lesions |
US14/206,322 Expired - Lifetime US9855307B2 (en) | 2001-05-23 | 2014-03-12 | Herbal compositions for the treatment of mucosal lesions |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US10/478,718 Expired - Lifetime US7563466B2 (en) | 2001-05-23 | 2002-05-22 | Herbal compositions for the treatment of mucosal lesions |
Family Applications After (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US12/417,111 Abandoned US20090186104A1 (en) | 2001-05-23 | 2009-04-02 | Herbal compositions for the treatment of mucosal lesions |
US12/941,535 Abandoned US20110052733A1 (en) | 2001-05-23 | 2010-11-08 | Herbal compositions for the treatment of mucosal lesions |
US14/206,322 Expired - Lifetime US9855307B2 (en) | 2001-05-23 | 2014-03-12 | Herbal compositions for the treatment of mucosal lesions |
Country Status (10)
Country | Link |
---|---|
US (5) | US7563466B2 (en) |
EP (1) | EP1395271B1 (en) |
JP (1) | JP4465155B2 (en) |
AT (1) | ATE417621T1 (en) |
CA (1) | CA2447180C (en) |
DE (1) | DE60230407D1 (en) |
ES (1) | ES2319968T3 (en) |
IL (1) | IL143318A0 (en) |
PT (1) | PT1395271E (en) |
WO (1) | WO2002094300A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130280355A1 (en) * | 2010-10-11 | 2013-10-24 | Indena S.P.A. | Formulations for the treatment of disorders of the upper respiratory tract |
Families Citing this family (37)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL143318A0 (en) * | 2001-05-23 | 2002-04-21 | Herbal Synthesis Corp | Herbal compositions for the treatment of mucosal lesions |
IL153124A (en) * | 2002-11-27 | 2010-06-30 | Herbal Synthesis Corp | Solid mucoadhesive composition |
EP1591125A1 (en) | 2004-04-19 | 2005-11-02 | Universitätsklinikum Freiburg | Pharmaceutical composition comprising extracts of lichens and hypericum |
BRPI0403688A (en) * | 2004-09-01 | 2006-05-02 | Herbarium Lab Botan Ltda | topical herbal compound for treatment of herpes |
ES2747729T3 (en) * | 2004-11-22 | 2020-03-11 | Izun Pharmaceuticals Corp | Oral administration device through the mucosa |
US20060115556A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplement drink containing xanthone extracts |
US20060115555A1 (en) * | 2004-12-01 | 2006-06-01 | Foulger Sidney W | Nutritional supplements containing xanthone extracts |
ITMI20042414A1 (en) * | 2004-12-17 | 2005-03-17 | Indena Spa | FORMULATION FOR THE TREATMENT OF AFFECTIONS OF THE FIRST RESPIRATORY ROUTES |
JP5024505B2 (en) * | 2005-03-25 | 2012-09-12 | ライオン株式会社 | Remedy for hyperlipidemia caused by periodontal disease, oral composition and oral medicine |
FR2884144B1 (en) * | 2005-04-07 | 2008-04-11 | Eric Peltier | COMBINATION OF A HISTOLOGICAL OR CYTOLOGICAL FIXER, AND ONE OR MORE PHOTOACTIVABLE COMPOUNDS OF THE FAMILY OF QUINONS, ESPECIALLY HYPERICINE, HYPOCRELLIN A AND HYPOCRELLINE B. |
DE102005019653A1 (en) | 2005-04-26 | 2006-11-02 | Henkel Kgaa | Plant extracts for halitosis, gingivitis or periodontitis |
US20070071840A1 (en) * | 2005-09-27 | 2007-03-29 | Sridevi Dhanaraj | Method for treatment of cartilage disorders with centella extract |
US7491414B2 (en) * | 2005-10-12 | 2009-02-17 | Gaia Herbs, Inc. | Anti-inflammatory substances extracted from Echinacea |
AU2013242845B2 (en) * | 2006-06-20 | 2015-09-03 | Izun Pharmaceuticals Corporation | Anti-inflammatory dissolvable film |
US8021696B2 (en) * | 2006-06-20 | 2011-09-20 | Izun Pharmaceuticals Corporation | Anti-inflammatory dissolvable film |
JP5513111B2 (en) | 2006-07-20 | 2014-06-04 | イズン ファーマシューティカルズ コーポレイション | Film delivery rinse |
EP1882473A1 (en) * | 2006-07-28 | 2008-01-30 | Indena S.P.A. | Use of anthocyanosides to prepare formulations for the treatment of mucositis induced by antitumoral drugs |
GB0625430D0 (en) * | 2006-12-20 | 2007-01-31 | Mars Uk Ltd | Composition |
JP5707655B2 (en) | 2008-07-22 | 2015-04-30 | イズン ファーマシューティカルズ, インコーポレイテッド | Topical anti-inflammatory combination |
EP2523675B1 (en) * | 2010-01-11 | 2019-03-06 | Vitro-Bio Sarl | New synergistic compositions for the treatment of topical viral infections |
EP2552466A1 (en) * | 2010-03-29 | 2013-02-06 | Reiner Rittinghausen | Composition containing components of echinacea, elder, and chamomile for treating common colds |
CN104394875B (en) | 2012-03-14 | 2018-12-04 | Izun制药公司 | For treating the novel method and composition of disease |
US8920855B1 (en) | 2012-10-30 | 2014-12-30 | Setem Hemth, Inc | Methods of topically treating tinnitus and related disorders |
ES2761429T3 (en) * | 2013-04-17 | 2020-05-19 | Global Health Solutions Ag | Antiviral pharmaceutical composition, containing an extract of Juncus acutus |
WO2015056160A1 (en) * | 2013-10-14 | 2015-04-23 | Izun Pharmaceuticals Ltd. | Methods for treatment of m-tor inhibitor-associated stomatitis |
JP6294773B2 (en) * | 2014-06-27 | 2018-03-14 | 株式会社ナールスコーポレーション | Oral preparation for prevention or treatment of oral mucosal disease |
RU2583885C1 (en) * | 2015-01-12 | 2016-05-10 | Сергей Витальевич Аверьянов | Ointment for treatment of cheilitis |
CN104758697A (en) * | 2015-04-20 | 2015-07-08 | 于风叶 | Traditional Chinese medicine powder for treating recurrent oral ulceration |
KR102393596B1 (en) | 2016-04-22 | 2022-05-04 | 리셉터 홀딩스, 인크. | Fast-acting plant-based medicinal compounds and nutritional supplements |
ITUA20163253A1 (en) * | 2016-05-09 | 2017-11-09 | Giacomo Bruzzesi | UNCARIA TOMENTOSA FOR DENTAL USE |
EA201892396A1 (en) | 2016-12-02 | 2019-04-30 | Ресептор Лайф Сайенсиз, Инк. | QUICKLY PRODUCTIVE PLANT MEDICINES AND BIOLOGICALLY ACTIVE ADDITIVES |
CN108524625A (en) * | 2018-05-31 | 2018-09-14 | 广州聚澜健康产业研究院有限公司 | Cloudy capsule of a kind of kidney tonifying benefit and preparation method thereof |
IT201800009621A1 (en) | 2018-10-19 | 2020-04-19 | Roberto Soldati | Ozonated phytotherapeutic composition for tissue and bone regeneration |
US20220118035A1 (en) * | 2019-01-10 | 2022-04-21 | Innovacorium, Inc. | Pharmaceutical delivery compositions and uses thereof |
IL302462A (en) * | 2020-10-28 | 2023-06-01 | Izun Pharmaceuticals Corp | Treatment of oral mucositis |
FR3124378A1 (en) * | 2021-06-24 | 2022-12-30 | Bobs Silver | Antiseptic composition for nasal administration |
US20230405044A1 (en) * | 2020-11-04 | 2023-12-21 | Bobs Silver | Antiseptic composition |
Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5162037A (en) * | 1988-04-01 | 1992-11-10 | Whitson Laboratories, Inc. | Magnetically influenced homeopathic pharmaceutical formulations, methods of their preparation and methods of their administration |
US5543154A (en) * | 1991-12-27 | 1996-08-06 | Merck & Co., Inc. | Controlled release nifedipine delivery device |
US5780046A (en) * | 1995-06-13 | 1998-07-14 | American Home Products Corporation | Oral formulations of S(+)-ibuprofen |
US5834000A (en) * | 1997-04-11 | 1998-11-10 | Yng-Wong; Quing Non | Antiviral and antimicrobial herbal complex |
US5977176A (en) * | 1995-06-27 | 1999-11-02 | Wise; Ronald D. | Compositions for the treatment of warts and herpes |
US6039949A (en) * | 1997-02-27 | 2000-03-21 | Campamed, Inc. | Method of preparation and composition of a water soluble extract of the plant species uncaria |
US6350784B1 (en) * | 1996-02-12 | 2002-02-26 | Meryl J. Squires | Antimicrobial prevention and treatment of human immunedeficiency virus and other infectious diseases |
US6428819B1 (en) * | 1996-12-15 | 2002-08-06 | David Lavie | Plant extracts for the preparation of pharmaceutical compositions for the treatment of hepatitis |
US20030003140A1 (en) * | 2001-02-28 | 2003-01-02 | Efrat Biopolymers Ltd. | Absorbable solid compositions for topical treatment of oral mucosal disorders |
US20040151789A1 (en) * | 2001-05-23 | 2004-08-05 | Levine William Z. | Herbal compositions for the treatment of mucosal lesions |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6146633A (en) * | 1973-05-07 | 2000-11-14 | The Ohio State University | Method for treatment of antigenically modified polypeptides |
JPS61165334A (en) | 1984-08-03 | 1986-07-26 | メデイサ−チ、エス、ア− | Inhibition for viral infection activity and composition |
US6355684B1 (en) | 1990-10-11 | 2002-03-12 | Meryl J. Squires | Antimicrobial treatment for herpes simplex virus and other infectious diseases |
JPH07506842A (en) * | 1993-03-02 | 1995-07-27 | ウニベルシダ・デ・バジャドリ | Double-stranded non-toxic ribosome inactivating protein (RIP), its production method and application |
KR100228873B1 (en) | 1997-03-24 | 1999-11-01 | 강재헌 | Water-soluble extract of asiaticoside and madecassoside isolated from centella asiatica, and a process for the isolation thereof |
JPH10279468A (en) | 1997-04-01 | 1998-10-20 | Nisshin Oil Mills Ltd:The | Skin preparation for external use |
FR2770776B1 (en) | 1997-11-07 | 2000-03-17 | Lvmh Rech | USES OF D-XYLOSE AND ITS ESTERS TO IMPROVE THE FUNCTIONALITY OF SKIN CELLS |
KR20060123663A (en) | 1999-08-27 | 2006-12-01 | 미시간 스테이트 유니버시티 | A composition containing natural cyclooxygenase inhibitors |
JP2001098263A (en) | 1999-09-30 | 2001-04-10 | Fancl Corp | Novel antioxidant composition and anti-inflammatory composition |
US7565466B2 (en) * | 2006-03-22 | 2009-07-21 | Infineon Technologies Ag | Memory including an output pointer circuit |
-
2001
- 2001-05-23 IL IL14331801A patent/IL143318A0/en unknown
-
2002
- 2002-05-22 US US10/478,718 patent/US7563466B2/en not_active Expired - Lifetime
- 2002-05-22 PT PT02733198T patent/PT1395271E/en unknown
- 2002-05-22 EP EP02733198A patent/EP1395271B1/en not_active Expired - Lifetime
- 2002-05-22 ES ES02733198T patent/ES2319968T3/en not_active Expired - Lifetime
- 2002-05-22 WO PCT/IL2002/000402 patent/WO2002094300A1/en active Application Filing
- 2002-05-22 DE DE60230407T patent/DE60230407D1/en not_active Expired - Lifetime
- 2002-05-22 JP JP2002591017A patent/JP4465155B2/en not_active Expired - Fee Related
- 2002-05-22 AT AT02733198T patent/ATE417621T1/en not_active IP Right Cessation
- 2002-05-22 CA CA2447180A patent/CA2447180C/en not_active Expired - Lifetime
-
2009
- 2009-04-02 US US12/417,106 patent/US8075926B2/en not_active Expired - Fee Related
- 2009-04-02 US US12/417,111 patent/US20090186104A1/en not_active Abandoned
-
2010
- 2010-11-08 US US12/941,535 patent/US20110052733A1/en not_active Abandoned
-
2014
- 2014-03-12 US US14/206,322 patent/US9855307B2/en not_active Expired - Lifetime
Patent Citations (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5162037A (en) * | 1988-04-01 | 1992-11-10 | Whitson Laboratories, Inc. | Magnetically influenced homeopathic pharmaceutical formulations, methods of their preparation and methods of their administration |
US5543154A (en) * | 1991-12-27 | 1996-08-06 | Merck & Co., Inc. | Controlled release nifedipine delivery device |
US5780046A (en) * | 1995-06-13 | 1998-07-14 | American Home Products Corporation | Oral formulations of S(+)-ibuprofen |
US5977176A (en) * | 1995-06-27 | 1999-11-02 | Wise; Ronald D. | Compositions for the treatment of warts and herpes |
US6350784B1 (en) * | 1996-02-12 | 2002-02-26 | Meryl J. Squires | Antimicrobial prevention and treatment of human immunedeficiency virus and other infectious diseases |
US6428819B1 (en) * | 1996-12-15 | 2002-08-06 | David Lavie | Plant extracts for the preparation of pharmaceutical compositions for the treatment of hepatitis |
US6039949A (en) * | 1997-02-27 | 2000-03-21 | Campamed, Inc. | Method of preparation and composition of a water soluble extract of the plant species uncaria |
US5834000A (en) * | 1997-04-11 | 1998-11-10 | Yng-Wong; Quing Non | Antiviral and antimicrobial herbal complex |
US20030003140A1 (en) * | 2001-02-28 | 2003-01-02 | Efrat Biopolymers Ltd. | Absorbable solid compositions for topical treatment of oral mucosal disorders |
US20040151789A1 (en) * | 2001-05-23 | 2004-08-05 | Levine William Z. | Herbal compositions for the treatment of mucosal lesions |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US20130280355A1 (en) * | 2010-10-11 | 2013-10-24 | Indena S.P.A. | Formulations for the treatment of disorders of the upper respiratory tract |
US9168276B2 (en) * | 2010-10-11 | 2015-10-27 | Indena S.P.A. | Formulations for the treatment of disorders of the upper respiratory tract |
Also Published As
Publication number | Publication date |
---|---|
CA2447180C (en) | 2014-07-08 |
US20040151789A1 (en) | 2004-08-05 |
DE60230407D1 (en) | 2009-01-29 |
ATE417621T1 (en) | 2009-01-15 |
US20110052733A1 (en) | 2011-03-03 |
US8075926B2 (en) | 2011-12-13 |
US20140193345A1 (en) | 2014-07-10 |
WO2002094300A1 (en) | 2002-11-28 |
EP1395271A1 (en) | 2004-03-10 |
EP1395271B1 (en) | 2008-12-17 |
JP2004530698A (en) | 2004-10-07 |
CA2447180A1 (en) | 2002-11-28 |
IL143318A0 (en) | 2002-04-21 |
ES2319968T3 (en) | 2009-05-18 |
US7563466B2 (en) | 2009-07-21 |
US20090186104A1 (en) | 2009-07-23 |
JP4465155B2 (en) | 2010-05-19 |
PT1395271E (en) | 2009-03-23 |
US9855307B2 (en) | 2018-01-02 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US9855307B2 (en) | Herbal compositions for the treatment of mucosal lesions | |
KR101337578B1 (en) | Mucoadhesive xyloglucan―containing formulations useful in medical devices and in pharmaceutical formulations | |
US7943169B2 (en) | Absorbable solid compositions for topical treatment of oral mucosal disorders | |
US8980334B2 (en) | Double-layered absorbable solid compositions for the topical treatment of oral mucosal disorders | |
JP6410355B2 (en) | Novel methods and compositions for treating diseases | |
CN105833278B (en) | For treating the composition of xerostomia and mouth disease | |
CN105031083B (en) | Application of traditional Chinese medicine composition for preventing and treating oral ulcer in preparation of oral care product | |
JP3103373B2 (en) | Antivirals derived from Kukuinat skin | |
US20150297661A1 (en) | Analgesic compositions and methods of use | |
Maskare et al. | Novel formulation for treatment of mouth ulcer | |
Galal et al. | Therapeutic efficacy of herbal formulations for recurrent aphthous ulcer. correlation with salivary epidermal growth factor | |
Janani | Formulation and Evaluation of Antimicrobial Mucoadhesive Dental Gel of Aerial Root of Ficus Benghalensis L to Enhance the Therapeutic activity using Clove Oil | |
CN110859790B (en) | Application of traditional Chinese medicine composition in preparation of oral care product | |
CN102665745A (en) | Preventing or treating periodontal diseases by herbal extract | |
Hendiani et al. | The Effectiveness of Mangosteen Peel (Garcinia Mangostana L) Extract Mouthwash on Reducing Gingival Inflammation | |
CN111084741A (en) | Application of red peony root extract in preparation of oral care products | |
Schulz et al. | Skin, Trauma, Rheumatism, and Pain | |
CN110652501A (en) | Preparation method of propolis traditional Chinese medicine adhesive tablet with double-layer structure for oral cavity | |
CN111514176A (en) | Application of artemisia selengensis polyphenol extract in oral mucosa repair |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AS | Assignment |
Owner name: HERBAL SYNTHESIS CORPORATION, ISRAEL Free format text: ASSIGNMENT OF ASSIGNORS INTEREST;ASSIGNORS:LEVINE, WILLIAM Z.;SAFFER, ARON J.;FARAN, MINA;REEL/FRAME:022505/0490 Effective date: 20031116 Owner name: IZUN PHARMACEUTICALS CORPORATION, ISRAEL Free format text: CHANGE OF NAME;ASSIGNOR:HERBAL SYNTHESIS CORPORATION;REEL/FRAME:022513/0198 Effective date: 20050131 |
|
ZAAA | Notice of allowance and fees due |
Free format text: ORIGINAL CODE: NOA |
|
ZAAB | Notice of allowance mailed |
Free format text: ORIGINAL CODE: MN/=. |
|
ZAAA | Notice of allowance and fees due |
Free format text: ORIGINAL CODE: NOA |
|
ZAAB | Notice of allowance mailed |
Free format text: ORIGINAL CODE: MN/=. |
|
STCF | Information on status: patent grant |
Free format text: PATENTED CASE |
|
FEPP | Fee payment procedure |
Free format text: PAYOR NUMBER ASSIGNED (ORIGINAL EVENT CODE: ASPN); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
FPAY | Fee payment |
Year of fee payment: 4 |
|
AS | Assignment |
Owner name: HAHN, ELLIOT F, FLORIDA Free format text: SECURITY AGREEMENT;ASSIGNOR:IZUN PHARMACEUTICALS CORPORATION;REEL/FRAME:040824/0202 Effective date: 20161201 |
|
AS | Assignment |
Owner name: HAHN, ELLIOT F, FLORIDA Free format text: CORRECTIVE ASSIGNMENT TO CORRECT THE APPLICATION NUMBERS 14193345 AND 15006421 PREVIOUSLY RECORDED AT REEL: 040824 FRAME: 0202. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY AGREEMENT;ASSIGNOR:IZUN PHARMACEUTICALS CORPORATION;REEL/FRAME:045032/0099 Effective date: 20161201 |
|
AS | Assignment |
Owner name: HAHN, ELLIOT F, FLORIDA Free format text: RELEASE BY SECURED PARTY;ASSIGNOR:IZUN PHARMACEUTICALS CORPORATION;REEL/FRAME:047934/0363 Effective date: 20161201 |
|
MAFP | Maintenance fee payment |
Free format text: PAYMENT OF MAINTENANCE FEE, 8TH YR, SMALL ENTITY (ORIGINAL EVENT CODE: M2552); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY Year of fee payment: 8 |
|
AS | Assignment |
Owner name: JONATHAN KALMAN, ISRAEL Free format text: SECURITY INTEREST;ASSIGNOR:IZUN PHARMACEUTICALS CORPORATION;REEL/FRAME:056716/0583 Effective date: 20210610 |
|
FEPP | Fee payment procedure |
Free format text: MAINTENANCE FEE REMINDER MAILED (ORIGINAL EVENT CODE: REM.); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
LAPS | Lapse for failure to pay maintenance fees |
Free format text: PATENT EXPIRED FOR FAILURE TO PAY MAINTENANCE FEES (ORIGINAL EVENT CODE: EXP.); ENTITY STATUS OF PATENT OWNER: SMALL ENTITY |
|
STCH | Information on status: patent discontinuation |
Free format text: PATENT EXPIRED DUE TO NONPAYMENT OF MAINTENANCE FEES UNDER 37 CFR 1.362 |
|
FP | Lapsed due to failure to pay maintenance fee |
Effective date: 20231213 |